Americans live in a culture that glorifies youth. According to market researcher FIND/SVP, the anti- aging products market is expected to hit $56 billion by 2007. Studies in post-menopausal women have found that hormone replacement therapy is effective at reversing the dryness and wrinkling that affects aging skin. Based on these studies, there is increasing interest in the use of topical creams containing hormones such as estrogen to prevent or reverse some of the normal cutaneous aging processes in younger pre-menopausal women. While exposure to these creams may be beneficial cosmetically, the effect of applying estrogen to sun exposed sites for prolonged periods of time, on skin cancer development is not known. Our preliminary studies using female Skh-1 hairless mice found a significant increase in the number of tumors in mice treated topically with estrogen immediately following UVB exposure compared to mice treated with vehicle control. These data indicate that increased levels of estrogen in the skin combined with UV exposure may act to enhance initiation and promotion of UV-induced skin cancers. These findings also suggest that the use of lotions and creams containing estrogenic compounds on sun exposed sites by younger women may be contributing to the increase in the number of skin tumors being diagnosed in women under the age of 40. Most studies have examined the effects of topical or systemic estrogen on the skin in post-menopausal women, however the reality is that younger pre-menopausal women are applying topical estrogen containing creams on their faces previously exposed to UV light to prevent/reverse the signs of aging. Two specific aims are proposed to test the hypothesis that topical estrogen application to previously UVB exposed skin accelerates skin carcinogenesis. Studies in specific aim 1 will use the Skh-1 hairless mouse murine model of UVB induced skin carcinogenesis to determine the effects of clinically used topically applied estrogen (Estrogel(R)) on UVB induced skin tumor development in previously UVB exposed female skin of intact (pre-menopausal) and ovariectomized (post-menopausal) mice. Studies in specific aim 2 will determine the effects of topically applied estrogen (Estrogel(R)) on UVB induced skin tumor progression in female Skh-1 skin of intact and ovariectomized mice. The studies carried out in these aims will determine whether topical estrogen increases the number of UVB induced skin tumors that develop and also whether it differentially enhances the progression of benign UVB-induced tumors to malignant squamous cell carcinomas in intact (pre-menopausal) and ovariectomized (post-menopausal) mice. PUBLIC HEALTH RELEVANCE: There is an increase societal pressure in the US to remain young looking. Several studies carried out in post-menopausal women demonstrate the effectiveness of topical estrogen in reversing the signs of aging including thinning, dryness and wrinkling. As a result younger pre- and peri-menopausal women are turning to topical creams containing estrogen as anti-aging lotions. Our preliminary studies using female Skh-1 hairless mice found a significant increase in the number of tumors in mice treated topically with estrogen immediately following UVB exposure compared to mice treated with vehicle control. These data indicate that increased levels of estrogen in the skin combined with UV exposure may act to enhance initiation and promotion of UV- induced skin cancers. These findings also suggest that the use of lotions and creams containing estrogenic compounds on sun exposed sites by younger women may be contributing to the increase in the number of skin tumors being diagnosed in women under the age of 40. The current studies are designed to determine the effect of topical estrogen treatment of previously UVB exposed skin on tumor development and progression from benign lesions to frank malignant squamous cell carcinomas.